Potassium Carbonate → N-(7-(2-chlorophenyl)-5-ethynyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

Temperature

50 °C

A mixture of N-(5-chloro-7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide (110 mg, 0.31 mmol), (trimethylsilyl)acetylene (45 mg, 0.46 mmol), N,N-diisopropylethylamine (0.1 mL, 0.61 mmol), copper(I) iodide (6 mg, 0.03 mmol), and bis(triphenylphosphine)palladium(II) chloride (15 mg, 0.02 mmol) in 1,4-dioxane (2 mL) was heated at 50° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was redissolved in methanol (4 mL) and treated with potassium carbonate (210 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 1 h, and then diluted with dichloromethane (100 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 12 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as a pale yellow solid (50 mg, 50%), which was used in the next step without further purification.

1. customThe cooled reaction mixture
2. washwashed with water (100 mL)
3. customThe organic layer was separated
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customevaporated in vacuo
7. customto afford a residue that
8. washwashed with water (100 mL)
9. customThe organic layer was separated
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. customevaporated in vacuo
13. customto afford a residue that
14. customwas purified by flash chromatography (silica, 12 g, ISCO, 0-50% ethyl acetate in heptane)

ORD record

ord-60082ab27c8343f7a2c1803199204847

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2